Debio 0123, a highly selective WEE1 inhibitor in adult patients with advanced solid tumors: A phase 1 dose escalation and expansion monotherapy study.
Abstract
TPS5634 Background: Debio 0123 is an oral, highly selective WEE1 inhibitor. WEE1 inhibition leads to S phase and G2/M cell cycle checkpoint bypass, allowing mitosis to occur without DNA repair, leading to mitotic catastrophe and cell death. This Phase 1 study (NCT05109975) is evaluating Debio 0123 monotherapy in patients with advanced solid tumors who have recurred or progressed following prior therapy and/or without available standard therapy. During the recently completed dose escalation, Debio 0123 was given once daily over a 21-day cycle and had a manageable safety profile with dose proportional pharmacokinetics. The recommended phase 2 dose is 260 mg (Papadopoulos, et al. ASCO2024,#2426). Methods: Following selection of RP2D, a 3-arm expansion phase is ongoing and currently enrolling patients, in both biomarker selected and unselected cohorts. Arm A includes patients with recurrent uterine serous carcinoma progressing after at least one prior line of platinum-based chemotherapy. Arm B includes patients with high-grade epithelial ovarian cancer, primary peritoneal cancer, or fallopian tube cancer that recurred to at least one prior line of platinum-based chemotherapy with high cyclin E1. Lastly, a biomarker-driven cohort (arm C) will enroll patients with specific locally advanced or metastatic solid tumors who have recurred or progressed following prior therapy and/or for whom no standard therapy is available. Additional key inclusion criteria are ECOG Performance Status 0-1, and measurable disease per RECIST 1.1. Debio 0123 will be administered once daily until disease progression, unacceptable toxicity, or withdrawal from the study. Primary endpoints are safety and tolerability and overall response rate (ORR) at recommended dose. Secondary endpoints include duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Enrolment is ongoing in Spain, Switzerland and US. Clinical trial information: NCT05109975 .
Article Details
Journal Info
Journal of Clinical Oncology
Lippincott Williams & Wilkins
Authors (20)
Maria M. Rubinstein
Memorial Sloan Kettering Cancer Center, New York, NY
Manish R. Sharma
START Center for Cancer Research—Midwest, Grand Rapids, MI
Kyriakos P. Papadopoulos
South Texas Accelerated Research Therapeutics, San Antonio
Maria-Pilar Barretina-Ginesta
Grupo Español de Investigación en Cáncer de Ovario (GEICO) and Medical Oncology Department, Institut Català d´Oncologia (ICO), Girona, Spain
Carmen Garcia-Duran
GEICO, Madrid, Spain
Mariano Ponz-Sarvise
Cancer Center Clínica Universidad de Navarra, Pamplona, Spain
Andres Redondo
From the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation (C.E.G., E.P.M., N.W., P.R., I.L.W., A.M.B.) and University of Pittsburgh School of Medicine–UPMC Hillman Cancer Center (C.E.G., N.W., P.R., A.M.B.) — both in Pittsburgh; AGO-B and Helios Klinikum Berlin–Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital, and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), Arbeitsgemeinschaft Gynäkologische Onkologie–Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen–EMN, Friedrich–Alexander University Erlangen–Nuremberg, Erlangen (P.A.F.), German Breast Group, Neu-Isenburg (P.W., S.L.), and the Center for Hematology and Oncology Bethanien, Goethe University, Frankfurt (S.L.) — all in Germany; National Taiwan University Hospital and National Taiwan University College of Medicine,...
Víctor Moreno
Denise S. Uyar
Froedtert & the Medical College of Wisconsin, Milwaukee, WI
Julian Wampfler
University of Bern, Bern, YT, Switzerland
Dagmar Hess
Luis Manso
Medical Oncology Division, Hospital Universitario 12 de Octubre, Madrid, Spain
Jeannette Fuchs
Debiopharm International SA, Lausanne, Switzerland
Emmelyne Dessein Corne
Debiopharm International SA, Lausanne, Switzerland
Noemie Luong
Debiopharm International SA, Lausanne, Switzerland
Vito Dozio
Debiopharm International SA, Lausanne, Switzerland
Tri Tat
Debiopharm International SA, Lausanne, Switzerland
Francoise Crevel
Debiopharm International SA, Lausanne, Switzerland
Victor Rodriguez Freixinos
Debiopharm International SA, Lausanne, Switzerland
Anastasios Stathis
Oncology Institute of Southern Switzerland, Ente Ospedaliero Cantonale, Bellinzoona, Switzerland